Oxygen is vital to all physiological processes. An insufficient supply of oxygen to implanted cells often leads to cell injury or death. Oxygen provision is a vital component in sustaining transplanted cells.
In healthy individuals, insulin release is regulated so as to maintain blood glucose levels in the range of about 70 to 110 milligrams per deciliter. In diabetics, insulin is either not produced at all (Type I diabetes), or the body cells do not properly respond to the insulin that is produced (Type II diabetes). The result is elevated blood glucose levels.
The success of many cellular transplants is compromised not only due to graft-host rejections, but also on account of ischemic conditions generated by insufficient oxygen supply to the transplant. Following implantation of the cells, oxygen is provided to the implanted cells from the body tissue (mainly via diffusion), and in some cases, from vascular structures that form around the transplanted cells with the help of angiogenic factors, e.g., VEGF and bFGF. However, the natural diffusion rate is too low to provide the cells with a significant, necessary amount of oxygen.
PCT Publication WO 01/50983 titled “IMPLANTABLE DEVICE”; to Vardi et al., and U.S. patent application Ser. No. 10/466,069 in the national phase thereof, which are incorporated herein by reference, describe an implantable device comprising a chamber for holding functional cells and an oxygen generator for providing oxygen to the functional cells.
In one embodiment, the oxygen generator is described as comprising photosynthetic cells that convert carbon dioxide to oxygen when illuminated. In another embodiment, the oxygen generator is described as comprising electrodes that produce oxygen by electrolysis.
US Patent Application Publication 2005/0136092 to Rotem, which is incorporated herein by reference, describes apparatus including a chamber, which is adapted to be implanted in a body of an individual, the chamber including functional cells and chlorophyll-containing elements comprising chlorophyll of an obligate photoautotroph. Typically, the chlorophyll-containing elements include intact photosynthetic cells and/or isolated chloroplasts. The chlorophyll-containing elements provide oxygen to the functional cells and/or consume carbon dioxide produced by the functional cells.
The chamber has one or more walls that are adapted to be permeable to nutrients and substances produced or secreted by the cells. The walls also typically immunoisolate the cells from constituents of the body. The chamber is adapted to be implanted under skin of the subject, or in the peritoneum. The apparatus further comprises a light source that is adapted to provide light to the chlorophyll-containing elements. The chamber may comprise an oxygen sensor that detects an oxygen concentration in vicinity of the functional cells, and/or in a vicinity of the chlorophyll-containing elements. Providing the light in the series of pulses generally reduces power consumption of the apparatus, and/or provides control of the quantity of oxygen produced by the chlorophyll-containing elements, and/or provides control of the quantity of carbon dioxide consumed by the chlorophyll-containing elements. In some embodiments of the invention, the chamber comprises an oxygen reservoir, which typically comprises a material that stores and releases oxygen, such as responsively to an oxygen concentration in a vicinity of the reservoir.
The oxygen reservoir typically stores oxygen produced by the chlorophyll-containing elements that is in excess of the current needs of the functional cells, and releases the stored oxygen if insufficient oxygen is later generated by the chlorophyll-containing elements.
PCT Publication WO 06/059322 to Evron et al., describes apparatus including a chamber which is adapted to be implanted in a body of an individual. The chamber includes functional cells and chlorophyll-containing elements comprising chlorophyll of an obligate photoautotroph. Other embodiments are also described.
U.S. Pat. No. 5,713,888 to Neuenfeldt et al., describes an implant assembly for a host tissue. The implant assembly comprises a pouch including wall means defining a chamber for holding a second member. The wall means includes an outer vascularizing membrane having a conformation that results in growth of vascular structures by the host tissue, close to an interface between the vascularizing membrane and host tissue. The assembly includes a second member that can be removably inserted in the chamber including an interior for receiving cells and wall means defining an immunoisolating membrane that isolates the cells from the immune response of the host tissue.
U.S. Pat. No. 6,368,592 to Colton et al., describes techniques for supplying oxygen to cells in vitro or in vivo by generating oxygen with an oxygen generator that electrolyzes water to oxygen and hydrogen.
U.S. Pat. No. 6,960,351 to Dionne et al., describes an immunoisolatory vehicle for the implantation into an individual of cells which produce a needed product or provide a needed metabolic function. The vehicle is comprised of a core region containing isolated cells and materials sufficient to maintain the cells, and a permselective, biocompatible, peripheral region free of the isolated cells, which immunoisolates the core yet provides for the delivery of the secreted product or metabolic function to the individual. The vehicle is described as being particularly well-suited to delivery of insulin from immunoisolated islets of Langerhans, and as being used advantageously for delivery of high molecular weight products, such as products larger than Immunoglobulin G (IgG).
US application 20090012502A1; titled “Oxygen Supply for Cell Transplant and Vascularization”; to Rotem Avi, et. al. describes an apparatus including a housing configured for insertion into a body of a patient; a photosynthetic oxygen supply configured to supply oxygen; and functional cells, coupled to the housing. The functional cells are adapted to receive the oxygen and to secrete at least one factor that induces vascularization in a vicinity of the housing when the housing is in the body of the patient. Other embodiments are also described.
PCT publication WO2009031154; titled “Air Gap For Supporting Cells”; to Stern Yaki, et. al. discloses an implantable medical device for transplanting functional pancreatic islet cells into subject for producing insulin, and providing oxygen to said transplanted cells. The device has housing comprising photosynthetic oxygen supplies and cells, and gas.
PCT publication WO2008062417; titled “Protecting Algae from Body Fluids”, to Rotem Avi, et. al. describes an apparatus for implantation into body of subject and providing oxygen to cells. The apparatus has isolated functional cells, photosynthetic elements, and semi-permeable barriers for protecting cells and elements from body fluid components.
U.S. Pat. No. 5,013,298; titled “Laterally compressed septum assembly and implantable infusion port with laterally compressed septum”; to Moden James, et. al. discloses a septum assembly port with elastomeric septum which can be penetrated by hypodermic needle.
The paper titled “High strength porous Ti-6A1-4V foams synthesized by solid state powder processing”; to Min Ha Lee, et. al; published in J. Phys. D: Appl. Phys. 41 (2008) 105404 (5pp); discloses production and high strength porous metal structures.
The following patents and patent applications may be of interest:
PCT Publication WO 07/138590 to Gross
U.S. Pat. No. 2,564,977 to Hu
U.S. Pat. No. 4,721,677 to Clark, Jr. et al.
U.S. Pat. No. 5,614,378 to Yang et al.
U.S. Pat. No. 6,268,161 to Han, et al.
U.S. Pat. No. 6,383,478 to Prokop, et al.
U.S. Pat. No. 6,630,154 to Fraker, et al.
US Patent Application Publication 2003/0113302 to Revazova et al.
US Patent Application Publication 2005/0025680 to Monzyk et al.
US Patent Application Publication 2006/0024276 to Ricordi et al.
The following articles may be of interest:
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